PDBsum entry 4l2h

Hydrolase

PDB id: 4l2h

Contents

Protein chain

436 a.a.

Ligands

AR6-AR6

Waters ×462

PDB id:

4l2h

Name:

Hydrolase

Title:

Structure of a catalytically inactive parg in complex with a poly-adp- ribose fragment

Structure:

Poly(adp-ribose) glycohydrolase. Chain: a. Engineered: yes. Mutation: yes

Source:

Tetrahymena thermophila. Organism_taxid: 5911. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.46Å R-factor: 0.140 R-free: 0.177

Authors:

A.Brassington,M.S.Dunstan,D.Leys

Key ref:

E.Barkauskaite et al. (2013). Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities. Nat Commun, 4, 2164. PubMed id: 23917065 DOI: 10.1038/ncomms3164

Date:

04-Jun-13 Release date: 24-Jul-13

Protein chain

I6L8L7  (I6L8L7_TETTH) -  poly(ADP-ribose) glycohydrolase from Tetrahymena thermophila

Seq: 457 a.a.

Struc: 436 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.2.1.143 - poly(ADP-ribose) glycohydrolase.
• Pathway: Poly(ADP-ribose) Glycohydrolase
• Reaction: [(1''->2')-ADP-alpha-D-ribose](n) + H2O = [(1''->2')-ADP-alpha-D- ribose](n-1) + ADP-D-ribose

[(1''->2')-ADP-alpha-D-ribose](n) + H2O = [(1''->2')-ADP-alpha-D- ribose](n-1) + ADP-D-ribose (Bound ligand (Het Group name = AR6) matches with 97.22% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1038/ncomms3164

Nat Commun 4:2164 (2013)

PubMed id: 23917065

Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities.

E.Barkauskaite, A.Brassington, E.S.Tan, J.Warwicker, M.S.Dunstan, B.Banos, P.Lafite, M.Ahel, T.J.Mitchison, I.Ahel, D.Leys.

ABSTRACT

Poly-ADP-ribosylation is a post-translational modification that regulates processes involved in genome stability. Breakdown of the poly(ADP-ribose) (PAR) polymer is catalysed by poly(ADP-ribose) glycohydrolase (PARG), whose endo-glycohydrolase activity generates PAR fragments. Here we present the crystal structure of PARG incorporating the PAR substrate. The two terminal ADP-ribose units of the polymeric substrate are bound in exo-mode. Biochemical and modelling studies reveal that PARG acts predominantly as an exo-glycohydrolase. This preference is linked to Phe902 (human numbering), which is responsible for low-affinity binding of the substrate in endo-mode. Our data reveal the mechanism of poly-ADP-ribosylation reversal, with ADP-ribose as the dominant product, and suggest that the release of apoptotic PAR fragments occurs at unusual PAR/PARG ratios.